RGD Reference Report - Cocaine withdrawal causes delayed dysregulation of stress genes in the hippocampus. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Cocaine withdrawal causes delayed dysregulation of stress genes in the hippocampus.

Authors: Garcia-Fuster, MJ  Flagel, SB  Mahmood, ST  Watson, SJ  Akil, H 
Citation: Garcia-Fuster MJ, etal., PLoS One. 2012;7(7):e42092. doi: 10.1371/journal.pone.0042092. Epub 2012 Jul 30.
RGD ID: 10445834
Pubmed: PMID:22860061   (View Abstract at PubMed)
PMCID: PMC3408429   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0042092   (Journal Full-text)

Relapse, even following an extended period of withdrawal, is a major challenge in substance abuse management. Delayed neurobiological effects of the drug during prolonged withdrawal likely contribute to sustained vulnerability to relapse. Stress is a major trigger of relapse, and the hippocampus regulates the magnitude and duration of stress responses. Recent work has implicated hippocampal plasticity in various aspects of substance abuse. We asked whether changes in stress regulatory mechanisms in the hippocampus may participate in the neuroadaptations that occur during prolonged withdrawal. We therefore examined changes in the rat stress system during the course of withdrawal from extended daily access (5-hours) of cocaine self-administration, an animal model of addiction. Tissue was collected at 1, 14 and 28 days of withdrawal. Plasma corticosterone levels were determined and corticosteroid receptors (GR, MR, MR/GR mRNA ratios) and expression of other stress-related molecules (HSP90AA1 and HSP90AB1 mRNA) were measured in hippocampal subfields using in situ hybridization. Results showed a delayed emergence of dysregulation of stress genes in the posterior hippocampus following 28 days of cocaine withdrawal. This included increased GR mRNA in DG and CA3, increased MR and HSP90AA1 mRNA in DG, and decreased MR/GR mRNA ratio in DG and CA1. Corticosterone levels progressively decreased during the course of withdrawal, were normalized following 28 days of withdrawal, and were correlated negatively with GR and positively with MR/GR mRNA ratio in DG. These results suggest a role for the posterior hippocampus in the neuroadaptations that occur during prolonged withdrawal, and point to a signaling partner of GR, HSP90AA1, as a novel dysregulated target during cocaine withdrawal. These delayed neurobiological effects of extended cocaine exposure likely contribute to sustained vulnerability to relapse.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
response to cocaine  IEP 10445834; 10445834 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Hsp90aa1  (heat shock protein 90 alpha family class A member 1)
Hsp90ab1  (heat shock protein 90 alpha family class B member 1)


Additional Information